thy/liv-SCID-hu mice: a system for investigating the in vivo effects of multidrug therapy on plasma viremia and human immunodeficiency virus replication in lymphoid tissues.
Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-hu mice were used to evaluate the in vivo efficacy of antiretroviral drugs. Ritonavir treatment alone initially suppressed plasma viremia, but the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, showing that the therapy did not completely suppress HIV infection in the thymic implant. When thy/liv-SCID-hu mice were treated with a combination of zidovudine, lamivudine, and ritonavir immediately after inoculation with HIV, cocultures of the thymic implants remained negative for HIV even 1 month after therapy was discontinued, suggesting that acute treatment can prevent the establishment of HIV infection. Thus, these modified thy/liv-SCID-hu mice should prove to be a useful system for evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.
Pettoello-Mantovani
M
M
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Kollmann
T R
TR
Katopodis
N F
NF
Raker
C
C
Kim
A
A
Yurasov
S
S
Wiltshire
H
H
Goldstein
H
H
D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002908:Chronic Disease; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D016332:Fetal Tissue Transplantation; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D016031:Liver Transplantation; D051379:Mice; D016513:Mice, SCID; D012367:RNA, Viral / Q000032:analysis / Q000097:blood / Q000187:drug effects; D012008:Recurrence; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019258:Saquinavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013950:Thymus Gland / Q000196:embryology / Q000637:transplantation; D014766:Viremia / Q000188:drug therapy*; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019258:Saquinavir; D019438:Ritonavir